1. Field of the Invention
The present invention is related to the synthesis of a novel pentacyclic compound. The pentacyclic compound is a useful intermediate in the synthesis of known tetracyclic antitumor compounds.
2. Discussion of the Background
Tetracyclic compounds having the general structure shown below ##STR1## and pharmaceutical salts thereof are known to have antitumor activity, antimicrobial activity, etc. and are useful for the treatment of tumors and infectious diseases in mammals. Such compounds, their synthesis and their use in treating infectious diseases and tumors are disclosed, for example, in U.S. Pat. No. 4,645,765 and U.S. application Ser. No. 06/947,759, filed Dec. 30, 1986.
The compound known as FR-No. 900482 shown below ##STR2## has been isolated from a culture broth of Streptomyces sandaensis and has been shown to exhibit potent antitumor activities . See (a) Iwami, M. et al; J. Antibiot., 1987, 40:589. (b) Kiyoto, S. et al; ibid. 1987, 40:594. (c) Shimomura, K. et al; ibid, 1987, 40:600. (d) Uchida, I. et al; J. Am. Chem. Soc., 1987, 109:4108. Biological testing against experimental tumors has shown that FR-No. 900482 has a similar activity to mitomycin C and is active against mytomycin C and vincristine-resistant P388 cells. Like mytomycin C, FR-No. 900482 is thought to be activated in the cells to form interstrand DNA-DNA cross-links (Masuda, K.; Nakamura, T.; Shimomura, K.; Shibata, T.; Terano, H.; Kohsaka, M., J. Antibiot., 1988, 41:1497). The organic synthesis of compounds such as FR-No. 900482 presents a formidable challenge to synthetic chemists due to the large number of asymmetric carbons and the presence of a labile hydroxyl amine moiety.
There continues to be a need for a new more efficient synthesis of potent antitumor and antimicrobial agents having intricate chemical structures in general. More specifically, a need exists for a new synthetic method for preparing antitumor agents having the general structure shown above.